Molecular biology of the gene
Biologists in the 20th century have
not only discovered the rules of genetics, but also the link between
genes and traits. The discovery of the structure of the DNA double
helix in 1953 has provided an explanation for both inheritance,
the faithful copying of genetic information during reproduction,
and the genetic code, the rules of how genetic information is read
and used to make proteins, the work horses of cells. Francis Crick,
the codiscoverer of the DNA structure, was also instrumental in
cracking the code. He proposed the central dogma of molecular biology
that says that genetic information flows from DNA via RNA to proteins.
Armed with this concept, molecular biologists soon found the codon
nature of the genetic code. A codon is a three letter DNA instruction
to use one particular amino acid in a protein. A string of codons
in a gene (nucleotide sequence) thus results in a string of amino
acids in a protein (amino acid sequence). This linear correspondence
of the molecule structure of a nucleic acid polymer to make a amino
acid polymer is universal. That means the same code is used in all
known organisms. In a few cases, the exact assignment of which codon
sequence is used for which amino acid differs. Differences are found
in organellar DNA (mitochondrion and chloroplasts) and DNA of some
microorganisms. The latter reflects on the enormous genetic diversity
of microorganisms, which is much broader than diversity among plants
and animals.
The central dogma of molecular biology
had soon to be modified when it was discovered that some viruses
contain RNA instead of DNA in their genome, and that they are able
to make a DNA copy after successfully infecting a host cell. They
use a protein called reverse transcriptase, an enzyme that revolutionized
molecular biology because it allows to make genes from RNA. This
particular process is now used to study gene expression patterns
in organisms and get an understanding of how organisms use their
genes to carry out their metabolic and physiological functions.
It also demonstrated the central role of RNA in modern organisms.
Together with proteins, they control how and when genes are being
used. Today, the central dogma means that genetic information flows
from nucleic acid to nucleic acid, and from nucleic acid to protein,
but never from protein to nucleic acid. While proteins have control
over the copying mechanism of nucleic acids, proteins cannot make
copies of themselves or independent of the genetic blueprint.
Other enzymes were also central to
advancement of genetic engineering. Restriction enzymes that recognize
short, but highly specific sequences allow the cutting of DNA into
smaller fragments, which in turn can be spliced together in any
combination with the help of ligases. Since the genetic code and
structure of DNA is universal, this cut and past technique allows
the recombination of DNA from different organisms, as different
as bacteria and humans. Recombinant DNA technology has allowed construction
of microorganisms, plants, and farm animals with particular novel
traits. Such genetically modified organisms provide better growth
conditions, longer shelf-life of grocery items, but also the development
of novel medicine. Genetic engineering has been particularly useful
for drug development and drug production. One of the first medical
applications of recombinant DNA technology was the production of
the human insulin (a protein) in bacterial cell culture. Here the
human gene with the instructions for the amino acid sequence of
insulin has been spliced into a bacterial DNA (plasmid). The bacterial
cells can be easily grown in large numbers and triggered to synthesize
and release the insulin protein for isolation and purification.
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Lukas K. Buehler |
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